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Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS
Author(s) -
Kadia Tapan M.,
Kantarjian Hagop,
Kornblau Steven,
Borthakur Gautam,
Faderl Stefan,
Freireich Emil J.,
Luthra Raja,
GarciaManero Guillermo,
Pierce Sherry,
Cortes Jorge,
Ravandi Farhad
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27596
Subject(s) - medicine , myeloid leukemia , cytarabine , myeloid , oncology , leukemia , targeted therapy , bone marrow , cancer research , immunology , cancer
BACKGROUND: Activating mutations in RAS are frequently present in patients with acute myeloid leukemia (AML), but their overall prognostic impact is not clear. METHODS: A retrospective analysis was performed to establish the clinical characteristics of patients with RAS ‐mutated ( RAS mut ) AML, to analyze their outcome by therapy, and to describe the proteomic profile of RAS mut compared with wild‐type RAS ( RAS WT ) AML. RESULTS: Of 609 patients with newly diagnosed AML, 11% had RAS mut . Compared with RAS WT , patients with RAS mut AML were younger (median age, 54 years vs 63 years; P = .001), had a higher white blood cell count (16K mm −3 vs 4K mm −3 ; P < 0.001) and bone marrow blast percentage (56% vs 42%; P = .01) at diagnosis, and were less likely to have an antecedent hematologic disorder (36% vs 50%; P = .03). The inv(16) karyotype was overrepresented in patients with RAS mut and the −5 and/or −7 karyotype was underrepresented. RAS mutations were found to have no prognostic impact on overall survival or disease‐free survival overall or within cytogenetic subgroups. There was a suggestion that patients with RAS mut benefited from cytarabine (AraC)‐based therapy. Proteomic analysis revealed simultaneous upregulation of the RAS ‐Raf‐MAP kinase and phosphoinositide 3‐kinase (PI3K) signaling pathways in patients with RAS mut . CONCLUSIONS: RAS mutations in AML may delineate a subset of patients who benefit from AraC‐based therapy and who may be amenable to treatment with inhibitors of RAS and PI3K signaling pathways. Cancer 2012. © 2012 American Cancer Society.

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